U.S. Pat. No. 7,105,530 disclosed pyrimidineamines and their derivatives thereof. These compounds are antineoplastic agents, and are useful in the treatment of various cancers and renal cell carcinoma. Among them pazopanib hydrochloride, chemically 5-[4-[N-(2,3-Dimethyl-2H-indazol-6-yl)-N-methylamino]pyrimidin-2-ylamino]-2-methylbenzenesulfonamide hydrochloride. Pazopanib hydrochloride is represented by the following structure:

Pazopanib hydrochloride is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR (Vascular endothelial growth factor receptors)-1, VEGFR-2, VEGFR-3, PDGFR (Platelet-derived growth factor receptors)-α/β, and c-kit that blocks tumor growth and inhibits angiogenesis. It has been approved for renal cell carcinoma by the U.S. Food and Drug Administration. Pazopanib hydrochloride may also be active in ovarian cancer and soft tissue sarcoma. Pazopanib hydrochloride also appears effective in the treatment of non-small cell lung carcinoma. Pazopanib hydrochloride is marketed under the brand name Votrient® by Glaxosmithkline in the form of tablet.
Processes for the preparation of pazopanib hydrochloride and related compounds were disclosed in U.S. Pat. No. 7,105,530 and U.S. Pat. No. 7,262,203.
According to U.S. Pat. No. 7,105,530, pazopanib hydrochloride can be prepared by reacting the N-(2-chloropyrimidin-4-yl)-N,2,3-trimethyl-2H-indazol-6-amine with 5-amino-2-methylbenzenesulfonamide in the presence of hydrochloric acid in isopropanol and ether.
U.S. patent application publication no. 2006/0252943 disclosed a process for the preparation of pazopanib hydrochloride. According to this patent, pazopanib hydrochloride can be prepared by reacting the N-(2-chloropyrimidin-4-yl)-N,2,3-trimethyl-2H-indazol-6-amine with 5-amino-2-methylbenzenesulfonamide in the presence of hydrochloric acid in ethanol or methanol or tetrahydrofuran or acetonitrile and dioxane.
We have discovered a novel process for the preparation of pazopanib using novel intermediate. The process of the invention results in higher yields compared with the known process.
We have also discovered a process for the purification of pazopanib hydrochloride.
Thus, one object of the present invention is to provide a novel process for preparing pazopanib and pharmaceutically acceptable acid addition salts of pazopanib in high yields using novel intermediate.
Another object of the present invention is to provide a process for the purification of pazopanib hydrochloride.